Severe local (injection site) toxicity is described for a number of antineoplastic drugs if inadvertently extravasated (delivered outside the vein) during administration. The goal of this proposed research is to (1) develop reproducible animal models for evaluating the skin toxicity produced by a variety of anti-cancer drugs currently in clinical use, (2) to conduct broad testing of potential local pharmacologic antidotes to reduce the extravasation toxicities of individual agents, (3) to characterize any effective interventions sufficiently to allow for the careful clinical application of any antidotal maneuver(s) which were effective in the animal model, and (4) to apply the toxicity-modeling technique and any antidote leads to new compounds which have a high potential for serious local toxicity prior to initiation into clinical trials. A partial list of locally toxic compounds would include drugs from the vinca alkaloid series (vincristine, vinblastine, vindesine) certain antitumor antibiotics (such as neocarzinostatin, mitomycin, mithramycin, streptozocin) especially the anthracycline series (doxorubicin, daunomycin, and many other experimental compounds such as AMSA and AD-32) and antitumor analogues such as methyl-GAG dacarbazine (DTIC). The methodology proposed for this study involves the intradermal (ID) injection of drugs and antidotes into hair-free sites on the dorsum of the mouse. Three lesion parameters are assessed: the area of induration, erythema and ulceration, with the data analyzed by computer using parametric (T-test) and non-parametric (ANOVA with subsequent multiple range tests) statistics. This established methodology (see publications) has already allowed several exciting leads to be isolated at the University of Arizona involving the pathogenesis and management of experimental doxorubicin and vinca alkaloid extravasation lesions.